CD62L as a Therapeutic Target in Chronic Lymphocytic Leukemia
CD62L as a Therapeutic Target in Chronic Lymphocytic Leukemia
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DOI：
10.1158/1078-0432.ccr-13-1037
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发表时间：
2013-10-15
影响因子：
11.5
通讯作者：
McMillan, Nigel A. J.
中科院分区：
文献类型：
--
作者：
Burgess, Melinda;Gill, Devinder;McMillan, Nigel A. J.
目的：尽管慢性淋巴细胞白血病（CLL）的治疗取得了进展，但这种疾病仍然无法用标准疗法治愈，复发是不可避免的。越来越多的证据表明，在肿瘤细胞的粘附特性的改变发挥了关键作用，在CLL.Experimental Design的发展和进展：71细胞表面分子的表达进行了检查CLL外周血单核细胞（PBMC）在培养3周以上。在体外以及淋巴结和骨髓活检中，进一步检查了最高度上调的标志物CD 62 L在CD 5（+）/CD 19（+）CLL细胞上的表达。CD 62 L的促生存作用进行了研究，使用功能性阻断抗体和治疗潜力的评价，通过比较与目前的化疗agents.Results：阻断CD 62 L导致细胞凋亡的CLL细胞，但不从健康供体的PBMC表明一种新的作用，CD 62 L在CLL细胞的生存。CLL细胞与骨髓基质细胞或内皮细胞共培养的有益效果不能保护CLL细胞免受抗CD 62 L相关毒性。此外，结合氟达拉滨或马磷酰胺与抗CD 62 L在体外产生的累加效应，无论有和没有stromal cells.Conclusion：这是第一次报道的数据表明，阻断激活和归巢标记，CD 62 L，调节CLL细胞的生存在体外。这些数据还表明，针对CD 62 L的治疗性抗体可以为接受当前标准化疗方案的CLL患者提供额外的临床益处。(C)2013年AACR。
Purpose: Despite advances in the treatment of chronic lymphocytic leukemia (CLL), the disease remains incurable with standard therapies and relapse is inevitable. A growing body of evidence indicates that alterations in the adhesion properties of neoplastic cells play a pivotal role in the development and progression of CLL.Experimental Design: The expression of 71 cell surface molecules was examined on CLL peripheral blood mononuclear cells (PBMCs) over 3 weeks in culture. The most highly upregulated marker, CD62L, was examined further for expression on CD5(+)/CD19(+) CLL cells in vitro and in lymph node and bone marrow biopsies. The prosurvival role of CD62L was examined using a functional blocking antibody and therapeutic potential evaluated by comparison with current chemotherapy agents.Results: Blocking CD62L resulted in apoptosis of CLL cells but not PBMCs from healthy donors suggesting a novel role for CD62L in CLL cell survival. The beneficial effect of coculturing CLL cells with bone marrow stromal cells or endothelial cells does not protect CLL cells from anti-CD62L-related toxicity. Moreover, combining fludarabine or mafosfamide with the anti-CD62L in vitro produced an additive effect both with and without stromal cells.Conclusion: This is the first reported data showing that blocking the activation and homing marker, CD62L, regulates CLL cell survival in vitro. These data also suggest that therapeutic antibodies against CD62L may provide additional clinical benefit to patients with CLL receiving current standard chemotherapy protocols. (C) 2013 AACR.